Gene therapy for lung cancer

Toshiyoshi Fujiwara, Noriaki Tanaka

Research output: Contribution to journalArticle

Abstract

This study was conducted to determine the feasibility, safety, humoral immune response, and biological activity of multiple intratumoral injections of Ad5CMV-p53, and to characterize the pharmacokinetics of Ad5CMV-p53 in patients with advanced non-small cell lung cancer (NSCLC). Fifteen patients with histologically confirmed NSCLC and p53 mutations were enrolled in our phase I trial. Nine patients received escalating dose levels of Ad5CMV-p53 (1 × 10 9 to 1 × 10 11 PFU [plaque-forming units]) as monotherapy once every 4 weeks. Six patients were treated on a 28-day schedule with Ad5CMV-p53 in combination with intravenous administration of cisplatin (80 mg/m 2). Patients were monitored for toxicity, vector distribution, antibody formation, and tumor response. Fifteen patients received a total of 63 intratumoral injections of Ad5CMV-p53 without dose-limiting toxicity. The most common treatment-related toxicity was a transient fever. Specific p53 transgene expression was detected using reverse-transcriptase polymerase chain reaction in biopsied tumor tissues throughout the period of treatment despite the presence of neutralizing anti-adenovirus antibody. Distribution studies revealed that the vector was detected in the gargle and plasma, but rarely in the urine. Thirteen of 15 patients were assessable for efficacy; one patient had a partial response (squamous cell carcinoma at the carina), 10 patients had stable disease, with three lasting ≧ 9 months, and 2 patients had progressive disease. Multiple courses of intratumoral Ad5CMV-p53 injection alone or in combination with intravenous administration of cisplatin were feasible and well tolerated in advanced NSCLC patients, and appeared to provide clinical benefit.

Original languageEnglish
Pages (from-to)270-279
Number of pages10
JournalBiotherapy
Volume20
Issue number3
Publication statusPublished - May 2006

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Genetic Therapy
Lung Neoplasms
Non-Small Cell Lung Carcinoma
Intravenous Administration
Cisplatin
Injections
Humoral Immunity
Neutralizing Antibodies
Reverse Transcriptase Polymerase Chain Reaction
Transgenes
Adenoviridae
Antibody Formation
Anti-Idiotypic Antibodies
Squamous Cell Carcinoma
Neoplasms
Appointments and Schedules
Fever
Pharmacokinetics
Urine
Safety

Keywords

  • Adenovirus
  • Apoptosis
  • Lung cancer
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Immunology and Allergy

Cite this

Fujiwara, T., & Tanaka, N. (2006). Gene therapy for lung cancer. Biotherapy, 20(3), 270-279.

Gene therapy for lung cancer. / Fujiwara, Toshiyoshi; Tanaka, Noriaki.

In: Biotherapy, Vol. 20, No. 3, 05.2006, p. 270-279.

Research output: Contribution to journalArticle

Fujiwara, T & Tanaka, N 2006, 'Gene therapy for lung cancer', Biotherapy, vol. 20, no. 3, pp. 270-279.
Fujiwara T, Tanaka N. Gene therapy for lung cancer. Biotherapy. 2006 May;20(3):270-279.
Fujiwara, Toshiyoshi ; Tanaka, Noriaki. / Gene therapy for lung cancer. In: Biotherapy. 2006 ; Vol. 20, No. 3. pp. 270-279.
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